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The FDA approved the injectable GIP/GLP-1 dual incretin-based agonist tirzepatide for chronic weight management among adults with obesity, according to a press release.
Tirzepatide (Zepbound, Eli Lilly) has been approved for use by adults with a BMI of 30 kg/m2 or higher or those with a BMI of 27 kg/m2 or higher plus one weight-related condition, such as high blood pressure, type 2 diabetes or higher cholesterol. The medication, which was previously approved under the name Mounjaro for use by adults with type 2 diabetes to improve glycemic control, should be used as an adjunct to a reduced calorie diet and increased physical activity.
Tirzepatide is a dual GIP/GLP-1 agonist that activates hormone receptors secreted in the intestines to reduce appetite and food intake. It is administered through a once-weekly injection under the skin. Dosage is increased over 4 to 20 weeks to achieve a target dose of either 5 mg, 10 mg or 15 mg.
Tirzepatide’s approval comes following the release of data from two randomized controlled trials. As Healio previously reported from the SURMOUNT-1 trial, adults with obesity and without diabetes were randomly assigned to receive 5 mg, 10 mg or 15 mg tirzepatide or placebo once-weekly for 72 weeks. At 72 weeks, all three tirzepatide groups achieved a mean weight loss of at least 15%, with the highest dose group losing 20.9% of their body weight. In the SURMOUNT-2 study, adults with obesity and type 2 diabetes were randomly assigned to receive 10 mg tirzepatide, 15 mg tirzepatide or placebo for 72 weeks. Adults receiving 10 mg tirzepatide lost 12.8% of their weight at 72 weeks, and those receiving 15 mg tirzepatide lost 14.7% of their weight.
In October, data from the SURMOUNT-3 and the SURMOUNT 4 trials were also presented. In SURMOUNT-3, adults with obesity lost a mean 24.3% of their weight with 12-week lifestyle intervention followed by 72 weeks of once-weekly tirzepatide. In the SURMOUNT-4 trial, adults receiving tirzepatide once-weekly for 36 weeks lost 20.2% of their body weight. Those who continued to receive tirzepatide up to 88 weeks in the study continued to lose weight, with a weight reduction of 25.3% at 88 weeks.
“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death, such as heart disease, stroke and diabetes,” John Sharretts, MD, director of the division of diabetes, lipid disorders and obesity in the FDA’s Center for Drug Evaluation and Research, said in the press release. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”
Adverse events with tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, allergic reactions, burping, hair loss and gastroesophageal disease.
According to the press release, tirzepatide causes thyroid C-cell tumors in rats, but it is unknown whether the medication causes such tumors in humans. Tirzepatide should not be used by people with a personal or family history of medullary thyroid cancer or people with multiple endocrine neoplasia syndrome type 2. Tirzepatide has also not been studied in people with a history of pancreatitis or severe gastrointestinal disease.
Obesity is a serious and life-threatening disease and it is good to have more tools in the tool kit that we can offer our high-risk patients. The GLP-1 receptor agonists and dual agonists, like tirzepatide, are game changers to help our patients. Despite lifestyle modification, which is always the foundation of any treatment plan, obesity is far more complicated than “calories in, calories out.” The brain regulates the body’s weight “set point,” and many of our patients are unable to get to a healthy weight to achieve their cardiometabolic health goals with lifestyle alone.
Obesity is strongly associated with serious CV complications — not only atherosclerotic CVD, but also heart failure, atrial fibrillation, sleep apnea and mortality. Data from LOOK AHEAD trial demonstrated that significant weight loss of 10% or more with lifestyle alone was associated with a significant reduction in major adverse CV events. We have seen similar data with weight loss after bariatric surgery and the use of GLP-1 receptor agonists. Topline results from the SELECT trial, which enrolled high-risk patients with overweight and obesity with established CVD, show semaglutide 2.4 mg reduced the risk for major adverse CV events by 20%. That is a large and meaningful reduction in risk. I suspect we will see similar results with tirzepatide; those trials are ongoing. For high-risk patients who have a lot of downstream CV risk factors related to overweight and obesity status, if you can address obesity, you can reduce CV events.
Dual agonists like tirzepatide are more potent in reducing weight with a similar side effect profile to the GLP-1 receptor agonists. This is important. The disease of obesity has not received the same level of attention as other chronic serious diseases. This is very stigmatizing. We do not say hypertension, for example, is a “lifestyle disease.” We treat it for CV risk reduction. We must also treat obesity for CV risk reduction because effective treatments now exist.
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